Tuesday, October 7, 2025 10/7/2025

Mechanisms of Target-Specific Axon Regeneration

Award Number: R00NS121595
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/15/2021
PERIOD OF PERFORMANCE END DATE: 02/28/2026

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Mechanisms of Target-Specific Axon Regeneration - Project Summary Nerve damage is a common affliction that causes sensory and/or motor deficits. Recovery involves a regenerative process in which damaged axons within a nerve fiber must re-extend to the appropriate target tissues, in a process known as target-specific regeneration. This process often fails in humans, leaving patients with chronic health problems. Improving clinical outcomes requires a better understanding of how target-specific regeneration is regulated. We know that components of the nerve support scaffold can guide axon re-extension along simple paths. However, when axons reach nerve branch points, they require more specific guidance mechanisms to differentiate between multiple paths and select the correct one. We have little understanding of what environmental cues guide these decisions, and how they are appropriately interpreted by regrowing axons. The objective of this proposal is to identify cellular and molecular mechanisms that regulate axon targeting decisions to promote target-specific regeneration. I have established the zebrafish vagus nerve as a model to elucidate mechanisms of target-specific axon regeneration. Regenerating vagus axons select between five nerve branches to robustly re-innervate the correct target tissue, although how they do so is not known. I hypothesize that two non-mutually-exclusive mechanisms regulate target-specific regeneration: 1) chemosensation, in which a regenerating axon can interpret spatially patterned chemical guidance cues in the environment that direct its growth; 2) fasciculation, in which a regenerating axon can recognize undamaged axons that are innervating its intended target and use them as a substrate for directed growth. The three aims of this proposal will comprehensively identify how growing axons interact with their environment at the cell biological and molecular levels during target-specific regeneration. In Aim 1, I will combine a novel single-cell chimera regeneration assay with live imaging and genetic and pharmacological manipulations to establish a conceptual understanding of how in vivo axon-environment interactions guide targeting decisions. In Aim 2, I will combine a novel method to label and isolate live neurons based on their innervation target with in vivo and in vitro techniques to precisely measure how axons of each of the five innervation target groups interact with other axons, and with chemical signals, in the environment. In Aim 3, I will combine innervation target-specific neuron isolation with RNAseq and mutant analysis for unbiased identification of molecules that regulate target selection in each of the five innervation target groups. This study will greatly enhance our fundamental understanding of how axons reinnervate their target tissues during regeneration, and provide an important knowledge base to develop improved treatments for nerve damage.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $224,101 )
2025	2025	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	3/6/2025	NON-COMPETING CONTINUATION	$224,101
														Subtotal = $224,101

Issue Date FY: 2024 ( Subtotal = $255,573 )
2024	2024	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	5	5/3/2024	NON-COMPETING CONTINUATION	$17,429
2024	2024	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	2/28/2024	NON-COMPETING CONTINUATION	$224,101
2024	2023	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	12/13/2023	EXTENSION WITH OR WITHOUT FUNDS	$14,043
														Subtotal = $255,573

Issue Date FY: 2023 ( Subtotal = $249,000 )
2023	2023	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	7/19/2023	EXTENSION WITH OR WITHOUT FUNDS	$249,000
														Subtotal = $249,000

Grand Total All Awards = $728,674

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Mechanisms of Target-Specific Axon Regeneration

Award Number: R00NS121595

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 12/15/2021

PERIOD OF PERFORMANCE END DATE: 02/28/2026

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